Chlorthalidone, i.e., 1-oxo-3-(3'-sulfamyl-4'-chlorophenyl)-3-hydroxyisoindoline, is a well known anti-hypertensive agent and is referenced on page 28 of The Merck Index, 9th Edition, 1976. Chlorthalidone and related compounds, hereinafter referred to for convenience as "isoindoline" compounds, and methods of preparation therefore are also disclosed in U.S. Pat. No. 3,055,904. Referring to the preparation of chlorthalidone itself for purposes of illustration, the '904 reference generally teaches that 2-(4'-chlorobenzoyl)benzoic acid (1) (Ind. & Eng. Chem. 369, 1929) is nitrated in the presence of sulfuric acid to form 2-(4'-chloro-3'-nitrophenyl)benzoic acid (2), the nitro group of (2) being subsequently reduced to an amine derivative (e.g., 2-(4'-chloro-3'-aminophenyl)benzoic acid) (3) which is diazotized to form a diazonium halide derivative (4), in turn decomposed in the presence of copper salts and sulfur dioxide to form a 2-(4'-chloro-3'-sulphochlorobenzoyl)benzoic acid, or 4-chloro- 2'-carboxy-benzophenone-3-sulphochloride (5). The latter compound can be treated with thionyl chloride to form the dichloride, i.e., 3-chloro-3-(3'-chlorosulfonyl-4'-chlorophenyl)phthalide (6) which is then treated with ammonia to form the desired isoindoline compound, in this case, 1-oxo-3-(3'-sulphamyl-4'-chlorophenyl)-3-hydroxyisoindoline.
The above noted procedure does, however, suffer disadvantages in that numerous process steps are required and that a hazardous diazotization step is necessarily employed. A synthesis method which has fewer total steps and which avoids the hazardous diazotization steps would thus be desirable and it is the principal object of the present invention to therefore provide a method which obviates such disadvantages.